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[Cancer Research 60, 22-27, January 1, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Increased p53-dependent Apoptosis by the Insulin-like Growth Factor Binding Protein IGFBP-3 in Human Colonic Adenoma-derived Cells1

Ann C. Williams2, Tracey J. Collard, Claire M. Perks, Paul Newcomb, Moganaden Moorghen, Jeff M. P. Holly and Chris Paraskeva

Cancer Research Campaign Colorectal Tumour Biology Research Group, Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD [A. C. W., T. J. C., M. M., C. P.], and Department of Surgery, Bristol Royal Infirmary, Bristol BS2 8HW [C. M. P., P. N., J. M. P. H.], United Kingdom

We investigated the expression of insulin-like growth factor binding protein 3 (IGFBP-3) in normal human colonic epithelium and whether IGFBP-3 is involved in the induction of apoptosis in colonic epithelial cells. A gradient of IGFBP-3 protein expression was observed within the normal colonic crypt, and increased IGFBP-3 expression was coincident with the region of increased differentiation and apoptosis. Treatment of human colonic tumor cell lines with IGFBP-3 alone was shown to have no effect on growth. However, an increase in p53-dependent apoptosis was observed in the presence of 100 ng/ml IGFBP-3 24 h after the induction of DNA damage by {gamma}-irradiation. These results suggest that IGFBP-3 enhances the p53-dependent apoptotic response of colorectal cells to DNA damage.




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Copyright © 2000 by the American Association for Cancer Research.